The invention relates generally to a device and method for preventing and treating diseases and more particularly to devices and methods for preventing and/or treating diseases with the application of ultrasound to targeted sites within a mammalian body. The present invention relates to devices and methods for preventing or treating cancers and other cell proliferative diseases such as arteriosclerosis, in mammals, by inducing or stimulating apoptosis within the target cells with ultrasonic energy. In particular, the devices and methods of the invention are useful in the stimulation of cell death and/or the inhibition of cell proliferation in cancer and other target cells. In the practice of the invention, ultrasonic energy can be further applied to antagonize the growth-factor-induced repression of apoptosis, to enhance the pro-apoptotic function of cytotoxic agents or hormonal or radiation therapy and/or to stimulate the pro-apoptotic actions of antioxidants.
Cancer is the second leading cause of death in the United States, accounting for approximately 450,000 deaths annually. Cancer is characterized primarily by an increase in the number of abnormal cells derived from a given normal tissue, invasion of adjacent tissues by these abnormal cells, and lymphatic or blood-borne spread of malignant cells to regional lymph nodes and to distant metastatic sites. Thus, insight into the complex events and strategies that lead from normal cellular growth and death to cancer, invasion and metastasis is important for the development of therapeutic strategies.
The complications of arteriosclerosis account for one half of all deaths in the United States and are the leading cause of permanent disability (Circulation 70:153A, 1984). A primary initiating factor in the formation of the atheromatous plaques is the proliferation of smooth muscle cells in the intima. Other conditions involving abnormal proliferation of target cells include vascular and fibrotic proliferative diseases, retinopathies, eczema or psoriasis. "Target cells" as used herein include, but are not limited to, precancerous cells, cancerous cells, cells having specific growth receptors and surrounding stromal cells in different tissues. The receptors for growth factors may include, but are not limited to, the epidermal growth factor (EGF), transforming growth factors (TGF alpha and beta), nerve growth factor (NGF), fibroblast growth factor (FGF), or insulin-like growth factors (IGF, I and II) or platelet-derived growth factor (PDGF).
Apoptosis is a mechanism by which cells are programmed to die under a wide range of physiological, biochemical and developmental stimuli. From the perspective of cancer, apoptosis is both a mechanism which suppresses tumorigenesis and is a predominant pathway in antineoplastic therapy. Many cancer cells circumvent the normal apoptotic mechanisms to prevent their self-destruction because of the many mutations they harbor. Thus, disarming apoptosis and other surveillance mechanisms is of fundamental significance in allowing the development of the malignant and metastatic phenotype of a cancer cell (Kerr, J. F. R. et al., 1994, Cancer 73:2013; and Williams, G. T., 1991, Cell 65:1097).
Apoptosis is also an important cellular response to a large variety of stress signals including, but not limited to, ionizing radiation, UV radiation, heat, growth factor deprivation, certain cytokines (like tumor necrosis factor (TNF) .alpha. and interferon (IFN) .beta.), as well as many chemotherapeutic drugs (Fisher, D. E., 1994, Cell 78:539-542). However, none of the modalities currently employed to induce apoptosis involve the use of ultrasonic energy.